Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(؉) group was significantly higher than in the HCV(؊) group (37% vs. 22%, P < .001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P ‫؍‬ .0001). Although survival has increased in the HCV(؊) group in recent years, it has significantly decreased in HCV recipients (P < .0001). The main cause of death among the latter was decompensated graft cirrhosis (n ‫؍‬ 23/105, 22%), whereas that of HCV(؊) patients was infections (n ‫؍‬ 10/52, 19%). Reasons for the recent worse outcome in HCV(؉) recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV(؉) recipients than among HCV(؊) ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome. (HEPATOLOGY 2002;36:202-210.) H epatitis C virus (HCV)-cirrhosis is the most frequent diagnosis in patients undergoing liver transplantation. 1 Viral recurrence is universal, 2 with development of histologic hepatitis in the majority of patients 3,4 and progression to cirrhosis in up to 30% after 5 years. 5,6 To date, however, most series have revealed no differences in patient or graft survival compared with uninfected controls. [3][4][5]7 Various reasons may explain these supposed discrepancies, one of which is the existence of different end points when assessing the effect of HCV infection on the graft. An indirect way to assess this effect is by calculating the rate of histologic progression posttransplantation, a task easily performed in the posttransplant setting because of the multiple biopsies generally performed and, through assessment of this rate, estimating the median time to development of graft cirrhosis. In one study, this duration was estimated to be 12 years, a duration significantly shorter than that described for the immunocompetent population. 6 From these data, one can anticipate an increase in HCV-related graft loss in the near future as transplant programs reach their second decade of activity. Our center follows a strict policy of performing annual li...

The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporinebased HCV-infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV-related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first-year liver biopsy findings. We studied 81 consecutive HCV-RNApositive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporinebased immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow-up was 32 months (range, 12-60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV-related cirrhosis at a median time of 24 months (range, 12-48 months), with an actuarial rate of HCV-cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P ‫؍‬ .02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P ‫؍‬ .001). The degree of activity and fibrosis score in the first-year biopsy were higher in patients who developed cirrhosis than in those who did not (P ‫؍‬ .008 and .18, respectively). Cirrhosis related to chronic infection with the hepatitis C virus (HCV) has emerged as one of the leading indications for orthotopic liver transplantation (OLT) worldwide, accounting for 50% of transplantation in Spain.

The natural history of clinically compensated hepatitis C virus (HCV) cirrhosis after liver transplantation is unknown. This information is relevant to transplant centers to improve the management of these patients and decide the optimal timing for retransplantation. The aims of the study were (1) to describe the natural history of patients with HCV-cirrhosis transplants in a center with annual liver biopsies, and (2) to determine predictors for clinical decompensation, retransplantation, and mortality rates. A total of 49 patients with HCV-graft cirrhosis, 39 clinically compensated at histologic diagnosis of cirrhosis (post-liver transplantation cirrhosis) were included and followed up for 1 year (15 days-3.5 years). All patients tested were infected with genotype 1b. Predictive variables included histologic activity index (HAI) at post-liver transplantation cirrhosis, liver function tests, age, sex, and maintenance immunosuppression. Eighteen of 39 patients developed at least 1 episode of decompensation after a median of 7.8 months (4 days-2.6 years; 93% ascites). The cumulative probability of decompensation was 8%, 17%, and 42% at 1, 6, and 12 months, respectively. Graft and patient survival rates were 100%, 85%, and 71% and 100%, 92%, and 74% at 1, 6, and 12 months, respectively. Patient survival rates dropped significantly once decompensation developed (93%, 61%, and 41% at 1, 6, and 12 months, respectively). Variables associated with decompensation, retransplantation, and mortality rate included a high Child-Pugh score (>A), low levels of albumin at post-liver transplantation cirrhosis, and a short interval between liver transplantation and post-liver transplantation cirrhosis. The natural history of clinically compensated HCV-graft cirrhosis is shortened when compared with immunocompetent patients. If retransplantation is considered, it should be performed promptly once decompensation develops. (HEPATOLOGY 2000;32:852-858.)

Transmission of hepatitis B virus (HBV) infection from T he acquisition of hepatitis B virus (HBV) infectionafter liver transplantation remains a significant problem in the liver transplant setting. Although de novo HBV infection may occur as a result of the reactivation of occult HBV infection in the recipient, 1,2 recent reports suggest that the vast majority of acquired HBV infections after liver transplantation are related to the donor liver. Liver grafts from donors who are hepatitis B surface antigen negative (HBsAg-) but positive for antibody to hepatitis B core antigen (anti-HBcϩ) have been shown to transmit HBV infection to HBsAg-liver transplant recipients at a rate that ranged from 33% to 78%. [3][4][5][6] However, these results were mostly derived from studies performed in geographic regions with a low prevalence (3% to 4%) of anti-HBc positivity in the liver donor population.The prevalence of HBsAg in the adult Spanish population ranges from 1.2% to 1.7%. 7,8 Accordingly, the prevalence of anti-HBc positivity in the general population is greater than that reported in areas of low prevalence of HBV infection. In a recent study, anti-HBc positivity was found in 10% of the Spanish adults aged 26 to 65 years. 7 In Spain, the current policy of the Organización Nacional de Trasplantes (ONT), the Spanish Organ Procurement Organization, is to test organ donors only for HBsAg. To a certain extent, the liver donor population is a reflection of the general population; therefore, it is reasonable to anticipate that the prevalence of anti-HBc positivity in Spanish liver donors and thus the incidence of de novo HBV infection after liver transplantation would be greater in our area than in areas of lower prevalence. In addition, inFrom the *HepatoGastroenterology, †Microbiology, and ‡Pathology Services, and the §Liver Transplantation and

Obesity, advanced age at infection, and elevated ALT levels predict rapid disease progression, suggesting that measures aimed at weight reduction may play a significant role in hepatitis C management. The natural history of hepatitis C is independent of the presence of autoimmunity markers.

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Controversy exists about the usefulness of yearly protocol liver biopsies after liver transplantation, mainly among patients with normal transaminase levels. The aim of this study is to determine (1) the prevalence and cause of histological liver injury in transplant recipients with a minimum histological follow-up of 1 year (n ‫؍‬ 254), and